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Breast cancer immunotherapy

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https://www.readbyqxmd.com/read/28080988/medical-mycology-and-fungal-immunology-new-research-perspectives-addressing-a-major-world-health-challenge
#1
REVIEW
Neil A R Gow, Mihai G Netea
Fungi cause more than a billion skin infections, more than 100 million mucosal infections, 10 million serious allergies and more than a million deaths each year. Global mortality owing to fungal infections is greater than for malaria and breast cancer and is equivalent to that owing to tuberculosis (TB) and HIV. These statistics evidence fungal infections as a major threat to human health and a major burden to healthcare budgets worldwide. Those patients who are at greatest risk of life-threatening fungal infections include those who have weakened immunity or have suffered trauma or other predisposing infections such as HIV...
December 5, 2016: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28079291/prognostic-value-of-pd-l1-in-breast-cancer-a-meta-analysis
#2
Changjun Wang, Hanjiang Zhu, Yidong Zhou, Feng Mao, Yan Lin, Bo Pan, Xiaohui Zhang, Qianqian Xu, Xin Huang, Qiang Sun
Programmed cell death 1 ligand 1 (PD-L1) is a promising therapeutic target for cancer immunotherapy. However, the correlation between PD-L1 and breast cancer survival remains unclear. Here, we present the first meta-analysis to investigate the prognostic value of PD-L1 in breast cancer. We searched Pubmed, Embase, and Cochrane Central Register of Controlled Trials databases for relevant studies evaluating PD-L1 expression and breast cancer survival. Fixed- and random-effect meta-analyses were conducted based on heterogeneity of included studies...
January 12, 2017: Breast Journal
https://www.readbyqxmd.com/read/28056464/impact-of-ctla-4-blockade-in-conjunction-with-metronomic-chemotherapy-on-preclinical-breast-cancer-growth
#3
Karla Parra, Paloma Valenzuela, Natzidielly Lerma, Alejandra Gallegos, Luis C Reza, Georgialina Rodriguez, Urban Emmenegger, Teresa Di Desidero, Guido Bocci, Mitchell S Felder, Marian Manciu, Robert A Kirken, Giulio Francia
BACKGROUND: Although there are reports that metronomic cyclophosphamide (CTX) can be immune stimulating, the impact of its combination with anti-CTLA-4 immunotherapy for the treatment of cancer remains to be evaluated. METHODS: Murine EMT-6/P breast cancer, or its cisplatin or CTX-resistant variants, or CT-26 colon, were implanted into Balb/c mice. Established tumours were monitored for relative growth following treatment with anti-CTLA-4 antibody alone or in combination with; (a) metronomic CTX (ldCTX; 20 mg kg(-1) day(-1)), b) bolus (150 mg kg(-1)) plus ldCTX, or (c) sequential treatment with gemcitabine (160 mg kg(-1) every 3 days)...
January 5, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28052005/bortezomib-augments-lymphocyte-stimulatory-cytokine-signaling-in-the-tumor-microenvironment-to-sustain-cd8-t-cell-antitumor-function
#4
Samuel T Pellom, Duafalia F Dudimah, Menaka C Thounaojam, Roman V Uzhachenko, Ashutosh Singhal, Ann Richmond, Anil Shanker
Tumor-induced immune tolerance poses a major challenge for therapeutic interventions aimed to manage cancer. We explored approaches to overcome T-cell suppression in murine breast and kidney adenocarcinomas, and lung fibrosarcoma expressing immunogenic antigens. We observed that treatment with a reversible proteasome inhibitor bortezomib (1 mg/kg body weight) in tumor-bearing mice significantly enhanced the expression of lymphocyte-stimulatory cytokines IL-2, IL-12, and IL-15. Notably, bortezomib administration reduced pulmonary nodules of mammary adenocarcinoma 4T1...
December 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/28049579/tumour-infiltrating-lymphocytes-and-the-emerging-role-of-immunotherapy-in-breast-cancer
#5
Stephen J Luen, Peter Savas, Stephen B Fox, Roberto Salgado, Sherene Loi
Breast cancer has not previously been considered a highly immunogenic cancer. Observations of tumour-infiltrating lymphocytes (TILs) in and around neoplastic cells in tumour samples, and associations with improved pathological complete response and clinical survival end points have changed our perspective on this. Lymphocytic infiltrates have long been observed in breast cancer; however, more recently, retrospective analysis of prospectively collected tissue samples from clinical trials has demonstrated the potential role of host immunosurveillance in influencing the biology of breast cancer...
December 31, 2016: Pathology
https://www.readbyqxmd.com/read/28042706/do-cdk4-6-inhibitors-have-potential-as-targeted-therapeutics-for-squamous-cell-cancers
#6
Nene N Kalu, Faye M Johnson
Introduction Dysregulation of cell cycle progression has an established link to neoplasia and cancer progression. Components of the cyclin D-CDK4/6-INK4-Rb pathway are frequently altered in squamous cell carcinomas (SCCs) by diverse mechanisms, including viral oncogene-induced degradation, mutation, deletion, and amplification. Activation of the CDK4/6 pathway may predict response to CDK4/6 inhibitors and provide clinical biomarkers. Recently, the CDK4/6 inhibitor palbociclib showed clinical efficacy in combination with cetuximab in HNSCC patients...
January 1, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28034454/comprehensive-genomic-sequencing-and-the-molecular-profiles-of-clinically-advanced-breast-cancer
#7
Jeffrey S Ross, Laurie M Gay
Targeting specific mutations that have arisen within a tumour is a promising means of increasing the efficacy of treatments, and breast cancer is no exception to this new paradigm of personalised medicine. Traditional DNA sequencing methods used to characterise clinical cancer specimens and impact treatment decisions are highly sensitive, but are often limited in their scope to known mutational hot spots. Next-generation sequencing (NGS) technologies can also test for these well-known hot spots, as well as identifying insertions and deletions, copy number changes such as ERBB2 (HER2) gene amplification, and a wide array of fusion or rearrangement events...
December 26, 2016: Pathology
https://www.readbyqxmd.com/read/28008921/reprogramming-the-immunological-microenvironment-through-radiation-and-targeting-axl
#8
Todd A Aguilera, Marjan Rafat, Laura Castellini, Hussein Shehade, Mihalis S Kariolis, Angela Bik-Yu Hui, Henning Stehr, Rie von Eyben, Dadi Jiang, Lesley G Ellies, Albert C Koong, Maximilian Diehn, Erinn B Rankin, Edward E Graves, Amato J Giaccia
Increasing evidence suggests that ionizing radiation therapy (RT) in combination with checkpoint immunotherapy is highly effective in treating a subset of cancers. To better understand the limited responses to this combination we analysed the genetic, microenvironmental, and immune factors in tumours derived from a transgenic breast cancer model. We identified two tumours with similar growth characteristics but different RT responses primarily due to an antitumour immune response. The combination of RT and checkpoint immunotherapy resulted in cures in the responsive but not the unresponsive tumours...
December 23, 2016: Nature Communications
https://www.readbyqxmd.com/read/28004985/cyclophosphamide-enhances-anti-tumor-effects-of-a-fibroblast-activation-protein-%C3%AE-based-dna-vaccine-in-tumor-bearing-mice-with-murine-breast-carcinoma
#9
Qiu Xia, Fei Geng, Fang-Fang Zhang, Chen-Lu Liu, Ping Xu, Zhen-Zhen Lu, Yu Xie, Bo Sun, Hui Wu, Bin Yu, Wei Kong, Xiang-Hui Yu, Hai-Hong Zhang
Cyclophosphamide (CY) is a DNA alkylating agent, which is widely used with other chemotherapy drugs in the treatment of various types of cancer. It can be used not only as a chemotherapeutic but also as an immunomodulatory agent to inhibit IL-10 expression and T regulatory cells (Tregs). Fibroblast activation protein α (FAPα) is expressed in cancer-associated fibroblasts in the tumor microenvironment. Immunotherapy based on FAPα, as a tumor stromal antigen, typically induces specific immune response targeting the tumor microenvironment...
December 22, 2016: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28003642/car-t-cell-therapy-of-solid-tumors
#10
REVIEW
Carmen S M Yong, Valerie Dardalhon, Christel Devaud, Naomi Taylor, Phillip K Darcy, Michael H Kershaw
The potential for immunotherapy as a treatment option for cancer is clear from remarkable responses of some leukemia patients to adoptive cell transfer using autologous T cells genetically modified to express chimeric antigen receptors (CARs). However, the vast majority of cancers, in particular the more common solid cancers, such as those of the breast, colon and lung, fail to respond significantly to infusions of CAR T cells. Solid cancers present some formidable barriers to adoptive cell transfer, including suppression of T cell function and inhibition of T cell localization...
December 22, 2016: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28002796/oncolytic-adenovirus-coexpressing-interleukin-12-and-decorin-overcomes-treg-mediated-immunosuppression-inducing-potent-antitumor-effects-in-a-weakly-immunogenic-tumor-model
#11
Eonju Oh, Il-Kyu Choi, JinWoo Hong, Chae-Ok Yun
Interleukin (IL)-12 is a potent antitumor cytokine. However, immunosuppressive tumor microenvironments containing transforming growth factor-β (TGF-β) attenuate cytokine-mediated antitumor immune responses. To enhance the efficacy of IL-12-mediated cancer immunotherapy, decorin (DCN) was explored as an adjuvant for overcoming TGF-β-mediated immunosuppression. We designed and generated a novel oncolytic adenovirus (Ad) coexpressing IL-12 and DCN (RdB/IL12/DCN). RdB/IL12/DCN-treated tumors showed significantly greater levels of interferon (IFN)-γ, tumor necrosis factor-α, monocyte chemoattractant protein-1, and IFN-γ-secreting immune cells than tumors treated with cognate control oncolytic Ad expressing a single therapeutic gene (RdB/DCN or RdB/IL12)...
December 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27999745/microrna-155-deficiency-impairs-dendritic-cell-function-in-breast-cancer
#12
Junfeng Wang, Stephen Iwanowycz, Fang Yu, Xuemei Jia, Shuilong Leng, Yuzhen Wang, Wei Li, Shiang Huang, Walden Ai, Daping Fan
In antitumor immunity, dendritic cells (DCs) capture, process, and present tumor antigens to T cells, initiating a tumoricidal response. However, DCs are often dysfunctional due to their exposure to the tumor microenvironment (TME), leading to tumor escape from immune surveillance. Here, a vital role of microRNA-155 (miR-155) in regulating the function of DCs in breast cancer is reported. Host miR-155 deficiency enhanced breast cancer growth in mice, accompanied by reduced DCs in the tumors and draining lymph nodes...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27993599/cd73-specific-sirna-loaded-chitosan-lactate-nanoparticles-potentiate-the-antitumor-effect-of-a-dendritic-cell-vaccine-in-4t1-breast-cancer-bearing-mice
#13
Farhad Jadidi-Niaragh, Fatemeh Atyabi, Ali Rastegari, Nasim Kheshtchin, Samaneh Arab, Hadi Hassannia, Maryam Ajami, Zahra Mirsanei, Sima Habibi, Farimah Masoumi, Farshid Noorbakhsh, Fazel Shokri, Jamshid Hadjati
The efficacy of conventional anti-tumor immunotherapeutic approaches is markedly affected by the immunosuppressive microenvironment of tumor. Since adenosine is one of the main orchestra leaders in immunosuppression symphony of tumor, targeting its producing molecules such as CD73 can help to achieve a better clinical outcome following conventional cancer immunotherapeutic approaches. In the present study, we evaluated the efficacy of CD73-specific siRNA-loaded chitosan-lactate nanoparticles (ChLa NPs) in combination with tumor lysate pulsed dendritic cells (DCs) vaccine in treatment of 4T1 (murine derived) breast cancer bearing mice...
December 18, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27990082/european-society-for-medical-oncology-2016-congress
#14
Walter Alexander
We review several key sessions from the European Society for Medical Oncology's annual congress, including those on emerging immunotherapies for melanoma and non-small-cell lung cancer and on treatments for renal, ovarian, and breast cancer.
December 2016: P & T: a Peer-reviewed Journal for Formulary Management
https://www.readbyqxmd.com/read/27987020/bio-hmgb1-from-breast-cancer-contributes-to-m-mdsc-differentiation-from-bone-marrow-progenitor-cells-and-facilitates-conversion-of-monocytes-into-mdsc-like-cells
#15
Zhaoliang Su, Ping Ni, Peng She, Yueqin Liu, Seidu A Richard, Wenlin Xu, Haitao Zhu, Jia Wang
Myeloid-derived suppressor cells (MDSC) constitute the major cell population that regulates immune responses. They are known to accumulate in tumors, chronic inflammatory and autoimmune diseases. Previous data indicate that high mobility group box 1(HMGB1) facilitates MDSC differentiation from bone marrow, suppresses NK cells, CD4(+) and CD8(+) T cells and is involved in cancer development. However, it remains unclear what potential mechanisms of HMGB1 facilitate MDSC differentiation. In the present work, we clearly demonstrate that HMGB1 secreted by cancer cells is N-glycosylated at Asn37, which facilitates monocytic (M)-MDSC differentiation from bone marrow via the p38/NFκB/Erk1/2 pathway and also contributes to conversion of monocytes into MDSC-like cells; HMGB1 blockade by a monoclonal antibody against the HMGB1 B box obviously reduced the accumulation of M-MDSC in tumor-bearing mice, delaying tumor growth and development; additionally, MDSC expansion and HMGB1 up-regulation were also found in breast cancer patients...
December 16, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27986267/-evaluation-of-the-immune-infiltrate-in-breast-cancer
#16
REVIEW
Nina Radosevic-Robin, Marie Béguinot, Frédérique Penault-Llorca
Tumour-infiltrating lymphocytes (TIL) are major components of the immune/"inflammatory" infiltrate found in tumour microenvironment. They reflect the intensity and the quality of the immune reaction to cancer. In breast cancer, TIL density and phenotypic profile have been demonstrated to be predictive of response to neoadjuvant treatment and of patient outcome. TIL density, currently the best-developed TIL-related biomarker, is defined as the percentage of tumour stroma surface occupied by TIL. The baseline TIL density of 50% and higher is associated with particularly high rates of pathological complete response to neoadjuvant therapy in triple negative and HER2+ breast cancer, as well as with significantly better recurrence-free and overall survival...
December 13, 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/27976881/photodynamic-therapy-mediated-by-nontoxic-core-shell-nanoparticles-synergizes-with-immune-checkpoint-blockade-to-elicit-antitumor-immunity-and-antimetastatic-effect-on-breast-cancer
#17
Xiaopin Duan, Christina Chan, Nining Guo, Wenbo Han, Ralph R Weichselbaum, Wenbin Lin
An effective, nontoxic, tumor-specific immunotherapy is the ultimate goal in the battle against cancer, especially the metastatic disease. Checkpoint blockade-based immunotherapies have been shown to be extraordinarily effective but benefit only the minority of patients whose tumors have been pre-infiltrated by T cells. Here, we show that Zn-pyrophosphate (ZnP) nanoparticles loaded with the photosensitizer pyrolipid (ZnP@pyro) can kill tumor cells upon irradiation with light directly by inducing apoptosis and/or necrosis and indirectly by disrupting tumor vasculature and increasing tumor immunogenicity...
December 28, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27974927/development-of-new-immunotherapy-treatments-in-different-cancer-types
#18
REVIEW
Stanculeanu Dl, Daniela Zob, Lazescu A, Bunghez R, Anghel R
Cancer immunotherapy involves the use of therapeutic modalities that determine a manipulation of the immune system by using immune agents such as cytokines, vaccines, cell therapies and humoral, transfection agents. Immunotherapy of cancer has to stimulate the host's anti-tumor response by increasing the effector cell number and the production of soluble mediators and decrease the host's suppressor mechanisms by inducing tumor killing environment and by modulating immune checkpoints. Immunotherapy seems to work better in more immunogenic tumors...
July 2016: Journal of Medicine and Life
https://www.readbyqxmd.com/read/27974697/surrogate-in-vitro-activation-of-innate-immunity-synergizes-with-interleukin-7-to-unleash-rapid-antigen-driven-outgrowth-of-cd4-and-cd8-human-peripheral-blood-t-cells-naturally-recognizing-muc1-her2-neu-and-other-tumor-associated-antigens
#19
Latha B Pathangey, Dustin B McCurry, Sandra J Gendler, Ana L Dominguez, Jessica E Gorman, Girish Pathangey, Laurie A Mihalik, Yushe Dang, Mary L Disis, Peter A Cohen
Effective adoptive immunotherapy has proved elusive for many types of human cancer, often due to difficulties achieving robust expansion of natural tumor-specific T-cells from peripheral blood. We hypothesized that antigen-driven T-cell expansion might best be triggered in vitro by acute activation of innate immunity to mimic a life-threatening infection. Unfractionated peripheral blood mononuclear cells (PBMC) were subjected to a two-step culture, first synchronizing their exposure to exogenous antigens with aggressive surrogate activation of innate immunity, followed by γ-chain cytokine-modulated T-cell hyperexpansion...
December 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27965307/dual-specific-chimeric-antigen-receptor-t-cells-and-an-indirect-vaccine-eradicate-a-variety-of-large-solid-tumors-in-an-immunocompetent-self-antigen-setting
#20
Clare Y Slaney, Bianca von Scheidt, Alexander J Davenport, Paul Beavis, Jennifer A Westwood, Sherly Mardiana, David Tscharke, Sarah Ellis, H Miles Prince, Joseph A Trapani, Ricky W Johnstone, Mark J Smyth, Michele W L Teng, Aesha Ali, Zhiya Yu, Steven A Rosenberg, Nicholas P Restifo, Paul J Neeson, Phillip K Darcy, Michael H Kershaw
PURPOSE: While adoptive transfer of T cells bearing a chimeric antigen receptor (CAR) can eliminate substantial burdens of some leukemias, the ultimate challenge remains the eradication of large solid tumors for most cancers. We aimed to develop an immunotherapy approach effective against large tumors in an immunocompetent, self-antigen preclinical mouse model. EXPERIMENTAL DESIGN: In this study, we generated dual-specific T cells expressing both a CAR specific for Her2 and a TCR specific for the melanocyte protein (gp100)...
December 13, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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